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Calculous Disease in Patients with Poliomyelitis
THE JOURNAL OF UROLOGY
Vol. 86, No. 5 November 1961 Copyright @ 1961 by The Williams & Wilkins Co. Printed in U.S.A.
CALCULOUS DISEASE IN PATIENTS WITH POLIOMYELITIS JAMES S. ELLIOT
AND
HAROLD E. TODD
From the Division of Urology, University of California Medical School, San Francisco, Cal. and the UrologySection, Oakland Veterans Administration Hospital, Oakland, Cal.
The major urological complication occurring in of the skeleton is generally considered to be the· patients severely paralyzed by poliomyelitis is most important factor in the high incidence of the development of urinary calculi. This was urolithiasis. The hypercalciuria of poliomyelitis. stressed by O'Connor and Weiner/ who found has been well documented by the studies of that urinary calculi develop in 35 per cent of such Dunning and Plum4 and Whedon and Shorr. 5 · patients. A similar incidence was observed by In totally paralyzed patients, the urinary excreTaylor, Alcock and Hildes. 2 The calculi are tion of calcium begins to increase about one· usually of the phosphatic type. In O'Connor and month after onset, rises to a peak, and graduallyWeiner's series, the calculi were all phosphatic, falls over a period of several months; in practias determined by chemical analysis. In our cally all cases, it reaches normal levels at the· series of 15 patients, 12 stones or 80 per cent were end of 1 year. Our own observations in this area composed of calcium phosphate or magnesium conform to previous reports. In figure 1 we have· ammonium phosphate. Calculi composed princi- compared the first indication of renal calculi by pally of calcium oxalate developed in only 3 x-ray with the time after onset and the degree of patients (table 1). This high incidence of phos- hypercalciuria. It is of interest to note that less. phatic stones is quite in contrast with the average than half of the patients in whom kidney stones. of 20 per cent as shown by Prien and Frondel. 3 developed did so during the first months of the Evidently there is something peculiar about disease, when hypercalciuria is at its maximum. poliomyelitis which predisposes toward the This observation suggests that some factors other formation of a phosphatic stone rather than the than increased urinary calcium may be of significommon oxalate type. It is our purpose to shed cance. Other factors which logically might besome light on this problem and to report the responsible for the formation of renal calculi. results of a combined clinical and laboratory are: 1) increased excretion of urinary phosphate, investigation with regard to phosphatic calculus 2) changes in the excretion of other salts, i.e. theformation. The basis of the report consists of a "salting in" or "ionic strength" effect, 3) change& study of forty-four adult patients with severe in the concentration or excretion of citric acid, paralysis due to poliomyelitis; among them 4) changes in urinary pH, 5) stasis incident to, fifteen or approximately one third, urinary calculi recumbency and 6) urinary infection. developed at some time in the course of their disease. All patients were seen at the Poliomyelitis THE EXCRETION OF PHOSPHATE Respiratory and Rehabilitation Center, Fairmont Hospital, San Leandro, California. The studies by Whedon and Shorr show that Body immobilization with loss of calcium and there is a transient increase in the excretion of phosphorus in the urine due to demineralization urinary phosphate which lasts only a short time, reaching its maximum on the fourteenth day Accepted for publication April 21, 1961. Read at annual meeting of Western Section, after onset and declining to normal levels within American Urological Association Inc., Las Vegas, three to four weeks and well before the urinary Nevada, February 6-9, 1961. Aided by a grant from the National Foundation excretion of calcium is significantly elevated. and U.S. Public Health Service grant No. A-4304. Studies of our own with regard to the urinary 1 O'Connor, J. J. Jr. and Wiener, L.: Urologic problems in postpoliomyelitic patients in res4 Dunning, M. F. and Plum, F.: Hypercalciuria pirators. J. A. M. A., 162: 164, 1956. 2 Taylor, J. R., Alcock, A. J. W. and Hildes, following poliomyelitis. Arch. Int. Med., 99: 716, 1957. J. A.: Urinary tract calculi in poliomyelitis. 5 Whedon, G. D. and Shorr, E.: Metabolic Canad. M.A. J., 75: 29, 1956. 3 Prien, E. L. and Frondel, C.: Studies in studies in paralytic acute anterior poliomyelitis. urolithiasis. I. The composition of urinary calculi. II. Alteration in calcium and phosphorus metabolism. J. Clin. Invest., 36: 966, 1957. J. Urol., 57: 949, 1947. 484
48b
CALCDLOUS DISEASE ASSOCIA'I'ED WITH POLIOi\llYELITIS
excretion of phosphorus in severely paralyzed patients have shown that after the first month of paralysis, urinary phosphorus drops to levels which a.re considerably below those of the average normal person. Tbe mean value of 24 hour urinary phosphorus for a series of patients, covering all stages of the disease, was .472 gm., com pa.red to an average normal of about 1 gm. It would seem, then, that an increased excretion of urinary phosphate cannot be implieated as a major factor in cnlculous disease in poliomyelitis patients. EXCRETION OF OTH}~R. INORGANIC SALTS IN URINE
The presence of other salts in urine, such as sodium, potassium, chloride, and sulfate, exert a. solublizing effect upon calcium phosphate and calcium oxalate. Chemically, this phenomenon is described as the "ionic strength." Other factors being equal, very dilute urine may be expected to dissolve less calcium phosphate than a more normally concentrated one. Reference to table 2 will show that the patients whom we have studied consistently excrete dilute urine with an average specific gravity of l.010, which is reflected by a very low urinary output of sodium, potassium, and chloride. Hyposthenuria, then, appears to be TABLE
l. Composition of iirinary calculi
Determined by
I
Cornposi tion
INumber
· - - - - 1 --·--·----------- - - - ·
Petrographic analysis of calculus
By dissolution with citric acid solution Presumed from typical x-ray appearance*
j
j
Apatite and struvite Apatit,e only Calcium oxalate phosphatic
3
Oxalate
l
Phosphatic
2
Total.
2
2 5
15 Phosphatic stones = 12 or 80%
* Initially, renal phosphatic calculi appear as multiple small spherules in the calyces and pelvis. Later, they coalesce into roughly rounded calculi and finally assume u. sta.ghorn pattern. Their appearance is quite distinctive from the calcium oxa.la.te calculus, which is more a.pt to be solitary and to show spicula radiating from the central core.
TABLE
2. A.verage 24-hov.r inorgan-ic salt cxcret·ion in normal persons ancl patients with poliomyelitis
-~--~----~-----~-
-····--······-·----
l\Jormal
Volume. Sp. Gr.. Ka (mEq). K (mEq). NH, (mEq). Mg (mg). Cl (mEq). S04 (gm.S.). p (gm.).
1543.
Poliomyeliti~
.78:-s
Hill. 1.010 .53. 5 31.3 200 1 101. 58 G .:31\)
1.056
+n
1.019 165.0
81.2 39. 1
124. 196.
a characteristic, and is a factor which will telld to reduce solubility of calcium salts in the urine. URINARY pH
Early in the course of our experience with thi8 disease, reports from the clinical indicated that the urine of virtually all c;evcrcly paralyzed patients was alkaline. careful investigation of urinary pH indicated that, severe paralysis was indeed associated with abnormally high urinary pH levels. The diurnal pH variations in patients were studied ,l8 scribed previously for normal persons. 6 of typical pH variation over the course of a hour period are shown in figure 2. pH curw~ as these occurred in the presence of sterile urim· and in the absence of urea-splitting bacteriul infection. An example of the diurnal variation~ in pH associated with an aetive urea-splitting bacterial urinary infection is indncled in t.he same figure. Furthn observations showed that :tn elevated diurnal. pH level occurred in who were totally paralyzed and to a lesser or not at all in patients who suffered onl? paralysis. The mean pH of 229 individual urine specimens collected from thirteen patients was 6.47. This may be compared to previously reported normal value of ::i.8.'S. possible causes for this phenomenon, wr; cu11sidered 1) hyperventilation and 2) diet. tiirwe most, if not all, patients who receive artificial respiration in a tank type respirator are intermittently hyperventilated, we Rtudiecl the effects of short term hyperventilation. T]m,e 6 .Elliot, J, S., Sharp, R. F. and Lewi,;, L Urinary pH. J. Urol., 81: ;:l:39, Hl59.
486
J. S. ELLIOT AND H. E. '.rODD
-.
•
STONE
•
·- - ·-
•
•
600
500 ~ ~
Q
"'
.
400
~ :E
~
300
...§ c.,
200 100
I
I
10 MONTHS
I
12
II I
I
16
20
24
11
111
I
I
4 YEARS
TIME AFTER ONSET
FIG. 1. Relation of urinary calcium excretion in quadriplegic patients to development of renal calculi. Each vertical bar represents 24-hour urinary calcium value. Dots at top indicate time of first appearance of renal calculus in individual patient.
./\\
;,,
·,
-..
! '\
\
\
1
!
.
.o\
.,........
\
.'
\l\ ,/
°'
\,_
'... ,;'
\ .
;-·. ,\; I
.,-'\
·,_,
\~
'
n ; \ ,,\ :\: V\ •
I
: \
''·,
\
I
/
\'
\
!
-.-.
\ ,, \ 4
\.
."
\
\
i\ ·------------
pH
!
·,
\,,..\
! ,, : ' \
"-,·,
\
:;\/
/4\ N !'•,
I\ ' 1
----,," -.
·1v~\
..................;
\ ..., 5.D
eoo
1000
1200
2:00
400
son
e.oo
10:00
12:00
2:00
4:0D
6:oo
s:oo
FIG. 2. Variations in urinary pH over 24 hour period in: A, normal person; B, paraplegic patient; C, quadriplegic patient; D, patient with ureasplitting urinary infection.
patients were placed on a constant diet over a period of days and their pH variations were determined over a 24 hour period both with and without hyperventilation. In each case, hyperventilation was established by ascertaining that the alveolar CO2 dropped to low levels. An example of the results obtained is shown by figure 3. This experiment indicated that hyperventilation is not a significant factor in the elevation of urinary pH. Although the patients under our observation were fed an average normal diet containing no more than H gm. calcium per day, the calculated acid-base ratio was approximately neutral. We found that patients who did not have flaccid paralysis responded to this diet with a normal acid urine excretion. Moreover, severely paralyzed patients placed upon an acid-ash diet responded by a change in urinary pH to a lesser degree than might be anticipated. On the other hand, the patients could excrete acid urine if they were given acid and they responded as expected to the administration of ammonium chloride or methionine with a normally acid urine. From these observations, we concluded that the abnormal urinary pH was not due to hyperventilation
CALCULOUS DIS.BJASE ASSOCIATED vVITH POLIOMYELITIS pH JS
A
, __ ------
W1tho,1I W1lf1
i ~~---~-
10
---1._ _
__j_ _ _ _ J____ j _
4
8
"i
L
'0
12
0 G
pH
B
78
-
Wilho,il
With
74 70
5.0
6.6
5.5
6.0
6.5
7 .0
7.5
pH 60
- - - - -- --.-4
/"
S.6
50 ~~-~~~~~-...L..---.....L...~'-........__l,_ ____, . , L _ ~
Som 10
12
4
8
10
12
2
4
6
8
FrG.
Variabons in 2°1 hour pH of 2 patients on constant die1. '"'''"''"'"''" made on · Each patient was hypr,rventilatecl for 2 honr period dnring one ,u·cu.'"'"''"" by solid line. Dotted line indica.tc,d hyperventil ati,,u.
Fro. 4. held in and at, the high, low nrinary phosphorus. based on graphic analysis of quantitaiivc · of urine speeimens ns described for salt solutions.
saturakd or M11n:,~:,,, during a of each 24 hour period, <,n:n though their rnlr:ium was in the normal range. ALTe;RATIONS IN CITRIC ACID EXCHl·'.'l'JON
nor to cfo, t p,,r se, nor to an to excrete acid but to the absence m the urine of acid metabolites which me the of n.rnsclc metabolism. As preYiously shown,7 tl1e dfcct of pH on the solubilit)· of calcium is more signifaant than changes of calcium concentration in urine. Reference to figmc 4 will show tlrn.t rtt a, pH of 6.0 and with an average phosphorus concentration, urine will be just saturn.ted or will hold in solution 160 mg . calcium per liter, a 24 hour urine of 1500 cc --240 mg. calcium. At a pH of 5.5 the 24 hour ,,a]uc would be 790 mg. calcium and at a of 6.6 it would be about 80 mg. <:alciurn. Assuming a low phosphorus output .such a.s occurs in poliomyclitis, the values would be 390 mg. calcium at 6.0 aml about (L5. Since the m 13 was it is that the mine of these patients was J S., Todd, lL IG . and .Lewis, L.: i:iome
calcium phosphate solubility. ,J. Urol. 1961
Along wit.h metabolic studies oI c:nlcium phosphorus excretion, Wlwdcm and Shoir'' measured tl1e urinary citric acid 111 who had had poliomyelitis and fowicl it to hr constant and within the i10rnt:1 I rnngta. I}IMOBILIZATION
The studies of Wh,-;clon and Shorr,' nnd J'lnm and Dunning" showed clearly that mohi.lization and even rnrly amlmlation, 1\·hl'n had no effect upon the urinctry e~cretion calcium in patients with poliomyelitis \cn,rtlieall of the under our obscrrntion were given a 1naximum of mobiliza.tion order to minimize the cffoets of recumlwnc:y upon 8 Whedon C D and Shorr studies in paralytic acute III. Metabolic and circulatory slowly oscillating bed . .J. Cliu.· [nvcst.
ID57. "Plttm, F and Dunning, i\L F. The therapeutic mobilization on calciuria aeute poliomyelitis. Arch. Int. 1\fo,L, 101: 19,58
488
J. S. ELLIOT AND H. E. TODD
urinary stasis. In spite of these efforts, the incidence of calculi in the patients we observed was roughly proportional to that of earlier reports. The real value of mobilization in preventing stasis and stone formation is difficult to evaluate since most of the patients under our observation received care in a different institution during the early phase of the disease. INFECTION
Probably the commonest cause of the formation of a phosphatic calculus in an otherwise normal person is the occurrence of urinary infection with an urea-splitting organism, such as B. proteus. It appears likely from previous studies that calculi containing struvite (magnesium ammonium phosphate) will develop only in the presence of this type of infection with its sustained high urinary pH. This agrees with the observations of Prien and Frondel3 and our own studies of struvite solubility.1° In the early report of Brady and Wilson, 11 the two calculi removed contained little or no calcium by chemical analysis. It seems likely that these stones were nearly pure struvite and due to urea-splitting infection. In our 12 patients with phosphatic calculi, all had infection associated with the development of stones, but in only 2 cases were the organisms urea-splitting. In 3 patients calcium oxalate calculi developed in the presence of sterile urine. In the other 29 patients 10 Elliot, J. S., Sharp, R. F. and Lewis, L.: The solubility of struvite in urine. J. Urol., 81: 366, 1959. 11 Brady, L. and Wilson, W. J.: Major urological surgery on poliomyelitic patients confined to respirators; discussion on etiology, prophylaxis against and treatment of calculi in recumbent patients. J. Urol., 61: 381, 1948.
in whom renal calculi did not develop, transient infection in the bladder was relatively common and often associated with small bladder stones, but evidence of acute or chronic renal infection was usually lacking. Presumably, infection of any sort in the renal pelvis and in the absence of urea-splitting organisms will produce an epithelial lesion and an increase in urinary mucoprotein which acts as a glue or binding agent leading to the retention of a nucleus or multiple nuclei. This observation agrees well with the work of Boyce and associates. 12 DISCUSSION AND SUMMARY
The high incidence of renal phosphatic calculi in severely paralyzed patients due to poliomyelitis appears to be related more to an elevated urinary pH than to hypercalciuria. In spite of skeletal demineralization, urinary phosphate is relatively low. The urine of quadriplegic patients is saturated with calcium phosphate during a good part of each 24 hour period and only the chance retention of a crystalline nucleus is required for calculus formation. In most instances, renal infection provides the mechanism for retention and growth of the nucleus of the calculus. Calcium oxalate calculi do occur in patients with poliomyelitis but are infrequent. Since they tend to occur in sterile urine, their formation may be related to hypercalciuria. However, significantly elevated urinary calcium values were not present in the 3 patients in our series. As in the case of calculi occurring in otherwise healthy persons, the chemical factors involved in the growth of a calcium oxalate calculus are poorly understood at the present time. 12 Boyce, W. H. and King, J. S.: Crystal-matrix interrelations in calculi. J. Urol., 81: 351, 1959.
Vol. 86, No. 5 November 1961 Copyright @ 1961 by The Williams & Wilkins Co. Printed in U.S.A.
CALCULOUS DISEASE IN PATIENTS WITH POLIOMYELITIS JAMES S. ELLIOT
AND
HAROLD E. TODD
From the Division of Urology, University of California Medical School, San Francisco, Cal. and the UrologySection, Oakland Veterans Administration Hospital, Oakland, Cal.
The major urological complication occurring in of the skeleton is generally considered to be the· patients severely paralyzed by poliomyelitis is most important factor in the high incidence of the development of urinary calculi. This was urolithiasis. The hypercalciuria of poliomyelitis. stressed by O'Connor and Weiner/ who found has been well documented by the studies of that urinary calculi develop in 35 per cent of such Dunning and Plum4 and Whedon and Shorr. 5 · patients. A similar incidence was observed by In totally paralyzed patients, the urinary excreTaylor, Alcock and Hildes. 2 The calculi are tion of calcium begins to increase about one· usually of the phosphatic type. In O'Connor and month after onset, rises to a peak, and graduallyWeiner's series, the calculi were all phosphatic, falls over a period of several months; in practias determined by chemical analysis. In our cally all cases, it reaches normal levels at the· series of 15 patients, 12 stones or 80 per cent were end of 1 year. Our own observations in this area composed of calcium phosphate or magnesium conform to previous reports. In figure 1 we have· ammonium phosphate. Calculi composed princi- compared the first indication of renal calculi by pally of calcium oxalate developed in only 3 x-ray with the time after onset and the degree of patients (table 1). This high incidence of phos- hypercalciuria. It is of interest to note that less. phatic stones is quite in contrast with the average than half of the patients in whom kidney stones. of 20 per cent as shown by Prien and Frondel. 3 developed did so during the first months of the Evidently there is something peculiar about disease, when hypercalciuria is at its maximum. poliomyelitis which predisposes toward the This observation suggests that some factors other formation of a phosphatic stone rather than the than increased urinary calcium may be of significommon oxalate type. It is our purpose to shed cance. Other factors which logically might besome light on this problem and to report the responsible for the formation of renal calculi. results of a combined clinical and laboratory are: 1) increased excretion of urinary phosphate, investigation with regard to phosphatic calculus 2) changes in the excretion of other salts, i.e. theformation. The basis of the report consists of a "salting in" or "ionic strength" effect, 3) change& study of forty-four adult patients with severe in the concentration or excretion of citric acid, paralysis due to poliomyelitis; among them 4) changes in urinary pH, 5) stasis incident to, fifteen or approximately one third, urinary calculi recumbency and 6) urinary infection. developed at some time in the course of their disease. All patients were seen at the Poliomyelitis THE EXCRETION OF PHOSPHATE Respiratory and Rehabilitation Center, Fairmont Hospital, San Leandro, California. The studies by Whedon and Shorr show that Body immobilization with loss of calcium and there is a transient increase in the excretion of phosphorus in the urine due to demineralization urinary phosphate which lasts only a short time, reaching its maximum on the fourteenth day Accepted for publication April 21, 1961. Read at annual meeting of Western Section, after onset and declining to normal levels within American Urological Association Inc., Las Vegas, three to four weeks and well before the urinary Nevada, February 6-9, 1961. Aided by a grant from the National Foundation excretion of calcium is significantly elevated. and U.S. Public Health Service grant No. A-4304. Studies of our own with regard to the urinary 1 O'Connor, J. J. Jr. and Wiener, L.: Urologic problems in postpoliomyelitic patients in res4 Dunning, M. F. and Plum, F.: Hypercalciuria pirators. J. A. M. A., 162: 164, 1956. 2 Taylor, J. R., Alcock, A. J. W. and Hildes, following poliomyelitis. Arch. Int. Med., 99: 716, 1957. J. A.: Urinary tract calculi in poliomyelitis. 5 Whedon, G. D. and Shorr, E.: Metabolic Canad. M.A. J., 75: 29, 1956. 3 Prien, E. L. and Frondel, C.: Studies in studies in paralytic acute anterior poliomyelitis. urolithiasis. I. The composition of urinary calculi. II. Alteration in calcium and phosphorus metabolism. J. Clin. Invest., 36: 966, 1957. J. Urol., 57: 949, 1947. 484
48b
CALCDLOUS DISEASE ASSOCIA'I'ED WITH POLIOi\llYELITIS
excretion of phosphorus in severely paralyzed patients have shown that after the first month of paralysis, urinary phosphorus drops to levels which a.re considerably below those of the average normal person. Tbe mean value of 24 hour urinary phosphorus for a series of patients, covering all stages of the disease, was .472 gm., com pa.red to an average normal of about 1 gm. It would seem, then, that an increased excretion of urinary phosphate cannot be implieated as a major factor in cnlculous disease in poliomyelitis patients. EXCRETION OF OTH}~R. INORGANIC SALTS IN URINE
The presence of other salts in urine, such as sodium, potassium, chloride, and sulfate, exert a. solublizing effect upon calcium phosphate and calcium oxalate. Chemically, this phenomenon is described as the "ionic strength." Other factors being equal, very dilute urine may be expected to dissolve less calcium phosphate than a more normally concentrated one. Reference to table 2 will show that the patients whom we have studied consistently excrete dilute urine with an average specific gravity of l.010, which is reflected by a very low urinary output of sodium, potassium, and chloride. Hyposthenuria, then, appears to be TABLE
l. Composition of iirinary calculi
Determined by
I
Cornposi tion
INumber
· - - - - 1 --·--·----------- - - - ·
Petrographic analysis of calculus
By dissolution with citric acid solution Presumed from typical x-ray appearance*
j
j
Apatite and struvite Apatit,e only Calcium oxalate phosphatic
3
Oxalate
l
Phosphatic
2
Total.
2
2 5
15 Phosphatic stones = 12 or 80%
* Initially, renal phosphatic calculi appear as multiple small spherules in the calyces and pelvis. Later, they coalesce into roughly rounded calculi and finally assume u. sta.ghorn pattern. Their appearance is quite distinctive from the calcium oxa.la.te calculus, which is more a.pt to be solitary and to show spicula radiating from the central core.
TABLE
2. A.verage 24-hov.r inorgan-ic salt cxcret·ion in normal persons ancl patients with poliomyelitis
-~--~----~-----~-
-····--······-·----
l\Jormal
Volume. Sp. Gr.. Ka (mEq). K (mEq). NH, (mEq). Mg (mg). Cl (mEq). S04 (gm.S.). p (gm.).
1543.
Poliomyeliti~
.78:-s
Hill. 1.010 .53. 5 31.3 200 1 101. 58 G .:31\)
1.056
+n
1.019 165.0
81.2 39. 1
124. 196.
a characteristic, and is a factor which will telld to reduce solubility of calcium salts in the urine. URINARY pH
Early in the course of our experience with thi8 disease, reports from the clinical indicated that the urine of virtually all c;evcrcly paralyzed patients was alkaline. careful investigation of urinary pH indicated that, severe paralysis was indeed associated with abnormally high urinary pH levels. The diurnal pH variations in patients were studied ,l8 scribed previously for normal persons. 6 of typical pH variation over the course of a hour period are shown in figure 2. pH curw~ as these occurred in the presence of sterile urim· and in the absence of urea-splitting bacteriul infection. An example of the diurnal variation~ in pH associated with an aetive urea-splitting bacterial urinary infection is indncled in t.he same figure. Furthn observations showed that :tn elevated diurnal. pH level occurred in who were totally paralyzed and to a lesser or not at all in patients who suffered onl? paralysis. The mean pH of 229 individual urine specimens collected from thirteen patients was 6.47. This may be compared to previously reported normal value of ::i.8.'S. possible causes for this phenomenon, wr; cu11sidered 1) hyperventilation and 2) diet. tiirwe most, if not all, patients who receive artificial respiration in a tank type respirator are intermittently hyperventilated, we Rtudiecl the effects of short term hyperventilation. T]m,e 6 .Elliot, J, S., Sharp, R. F. and Lewi,;, L Urinary pH. J. Urol., 81: ;:l:39, Hl59.
486
J. S. ELLIOT AND H. E. '.rODD
-.
•
STONE
•
·- - ·-
•
•
600
500 ~ ~
Q
"'
.
400
~ :E
~
300
...§ c.,
200 100
I
I
10 MONTHS
I
12
II I
I
16
20
24
11
111
I
I
4 YEARS
TIME AFTER ONSET
FIG. 1. Relation of urinary calcium excretion in quadriplegic patients to development of renal calculi. Each vertical bar represents 24-hour urinary calcium value. Dots at top indicate time of first appearance of renal calculus in individual patient.
./\\
;,,
·,
-..
! '\
\
\
1
!
.
.o\
.,........
\
.'
\l\ ,/
°'
\,_
'... ,;'
\ .
;-·. ,\; I
.,-'\
·,_,
\~
'
n ; \ ,,\ :\: V\ •
I
: \
''·,
\
I
/
\'
\
!
-.-.
\ ,, \ 4
\.
."
\
\
i\ ·------------
pH
!
·,
\,,..\
! ,, : ' \
"-,·,
\
:;\/
/4\ N !'•,
I\ ' 1
----,," -.
·1v~\
..................;
\ ..., 5.D
eoo
1000
1200
2:00
400
son
e.oo
10:00
12:00
2:00
4:0D
6:oo
s:oo
FIG. 2. Variations in urinary pH over 24 hour period in: A, normal person; B, paraplegic patient; C, quadriplegic patient; D, patient with ureasplitting urinary infection.
patients were placed on a constant diet over a period of days and their pH variations were determined over a 24 hour period both with and without hyperventilation. In each case, hyperventilation was established by ascertaining that the alveolar CO2 dropped to low levels. An example of the results obtained is shown by figure 3. This experiment indicated that hyperventilation is not a significant factor in the elevation of urinary pH. Although the patients under our observation were fed an average normal diet containing no more than H gm. calcium per day, the calculated acid-base ratio was approximately neutral. We found that patients who did not have flaccid paralysis responded to this diet with a normal acid urine excretion. Moreover, severely paralyzed patients placed upon an acid-ash diet responded by a change in urinary pH to a lesser degree than might be anticipated. On the other hand, the patients could excrete acid urine if they were given acid and they responded as expected to the administration of ammonium chloride or methionine with a normally acid urine. From these observations, we concluded that the abnormal urinary pH was not due to hyperventilation
CALCULOUS DIS.BJASE ASSOCIATED vVITH POLIOMYELITIS pH JS
A
, __ ------
W1tho,1I W1lf1
i ~~---~-
10
---1._ _
__j_ _ _ _ J____ j _
4
8
"i
L
'0
12
0 G
pH
B
78
-
Wilho,il
With
74 70
5.0
6.6
5.5
6.0
6.5
7 .0
7.5
pH 60
- - - - -- --.-4
/"
S.6
50 ~~-~~~~~-...L..---.....L...~'-........__l,_ ____, . , L _ ~
Som 10
12
4
8
10
12
2
4
6
8
FrG.
Variabons in 2°1 hour pH of 2 patients on constant die1. '"'''"''"'"''" made on · Each patient was hypr,rventilatecl for 2 honr period dnring one ,u·cu.'"'"''"" by solid line. Dotted line indica.tc,d hyperventil ati,,u.
Fro. 4. held in and at, the high, low nrinary phosphorus. based on graphic analysis of quantitaiivc · of urine speeimens ns described for salt solutions.
saturakd or M11n:,~:,,, during a of each 24 hour period, <,n:n though their rnlr:ium was in the normal range. ALTe;RATIONS IN CITRIC ACID EXCHl·'.'l'JON
nor to cfo, t p,,r se, nor to an to excrete acid but to the absence m the urine of acid metabolites which me the of n.rnsclc metabolism. As preYiously shown,7 tl1e dfcct of pH on the solubilit)· of calcium is more signifaant than changes of calcium concentration in urine. Reference to figmc 4 will show tlrn.t rtt a, pH of 6.0 and with an average phosphorus concentration, urine will be just saturn.ted or will hold in solution 160 mg . calcium per liter, a 24 hour urine of 1500 cc --240 mg. calcium. At a pH of 5.5 the 24 hour ,,a]uc would be 790 mg. calcium and at a of 6.6 it would be about 80 mg. <:alciurn. Assuming a low phosphorus output .such a.s occurs in poliomyclitis, the values would be 390 mg. calcium at 6.0 aml about (L5. Since the m 13 was it is that the mine of these patients was J S., Todd, lL IG . and .Lewis, L.: i:iome
calcium phosphate solubility. ,J. Urol. 1961
Along wit.h metabolic studies oI c:nlcium phosphorus excretion, Wlwdcm and Shoir'' measured tl1e urinary citric acid 111 who had had poliomyelitis and fowicl it to hr constant and within the i10rnt:1 I rnngta. I}IMOBILIZATION
The studies of Wh,-;clon and Shorr,' nnd J'lnm and Dunning" showed clearly that mohi.lization and even rnrly amlmlation, 1\·hl'n had no effect upon the urinctry e~cretion calcium in patients with poliomyelitis \cn,rtlieall of the under our obscrrntion were given a 1naximum of mobiliza.tion order to minimize the cffoets of recumlwnc:y upon 8 Whedon C D and Shorr studies in paralytic acute III. Metabolic and circulatory slowly oscillating bed . .J. Cliu.· [nvcst.
ID57. "Plttm, F and Dunning, i\L F. The therapeutic mobilization on calciuria aeute poliomyelitis. Arch. Int. 1\fo,L, 101: 19,58
488
J. S. ELLIOT AND H. E. TODD
urinary stasis. In spite of these efforts, the incidence of calculi in the patients we observed was roughly proportional to that of earlier reports. The real value of mobilization in preventing stasis and stone formation is difficult to evaluate since most of the patients under our observation received care in a different institution during the early phase of the disease. INFECTION
Probably the commonest cause of the formation of a phosphatic calculus in an otherwise normal person is the occurrence of urinary infection with an urea-splitting organism, such as B. proteus. It appears likely from previous studies that calculi containing struvite (magnesium ammonium phosphate) will develop only in the presence of this type of infection with its sustained high urinary pH. This agrees with the observations of Prien and Frondel3 and our own studies of struvite solubility.1° In the early report of Brady and Wilson, 11 the two calculi removed contained little or no calcium by chemical analysis. It seems likely that these stones were nearly pure struvite and due to urea-splitting infection. In our 12 patients with phosphatic calculi, all had infection associated with the development of stones, but in only 2 cases were the organisms urea-splitting. In 3 patients calcium oxalate calculi developed in the presence of sterile urine. In the other 29 patients 10 Elliot, J. S., Sharp, R. F. and Lewis, L.: The solubility of struvite in urine. J. Urol., 81: 366, 1959. 11 Brady, L. and Wilson, W. J.: Major urological surgery on poliomyelitic patients confined to respirators; discussion on etiology, prophylaxis against and treatment of calculi in recumbent patients. J. Urol., 61: 381, 1948.
in whom renal calculi did not develop, transient infection in the bladder was relatively common and often associated with small bladder stones, but evidence of acute or chronic renal infection was usually lacking. Presumably, infection of any sort in the renal pelvis and in the absence of urea-splitting organisms will produce an epithelial lesion and an increase in urinary mucoprotein which acts as a glue or binding agent leading to the retention of a nucleus or multiple nuclei. This observation agrees well with the work of Boyce and associates. 12 DISCUSSION AND SUMMARY
The high incidence of renal phosphatic calculi in severely paralyzed patients due to poliomyelitis appears to be related more to an elevated urinary pH than to hypercalciuria. In spite of skeletal demineralization, urinary phosphate is relatively low. The urine of quadriplegic patients is saturated with calcium phosphate during a good part of each 24 hour period and only the chance retention of a crystalline nucleus is required for calculus formation. In most instances, renal infection provides the mechanism for retention and growth of the nucleus of the calculus. Calcium oxalate calculi do occur in patients with poliomyelitis but are infrequent. Since they tend to occur in sterile urine, their formation may be related to hypercalciuria. However, significantly elevated urinary calcium values were not present in the 3 patients in our series. As in the case of calculi occurring in otherwise healthy persons, the chemical factors involved in the growth of a calcium oxalate calculus are poorly understood at the present time. 12 Boyce, W. H. and King, J. S.: Crystal-matrix interrelations in calculi. J. Urol., 81: 351, 1959.